Application of acupuncture methods goes back centuries. Today, there is much scientific research and many approaches to explain the mechanism of acupuncture. Among these approaches, the most popular one is the neurophysiologic approach. In this paper, we explain the series of events that follow the insertion of acupuncture needles under the headings of local reactions; regional reflexes related with viscero-cutaneous and cutaneo- visceral reflexes; increased levels of beta-endorphin, enkephalin, and serotonin in the central nervous system and plasma; and effects of these neurotransmitters in the nervous system and many other systems. We then address the clinical application of this neurophysiologic approach.